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1.
Sociol Health Illn ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152691

RESUMEN

Creative well-being is an increasing field of interest to which biomedical and social sciences have made uneven contributions. The instrumental value of culture and its subsequential public investment is grounded in the interplay of social, cultural and economic capital to attain and preserve wellbeing and health and foster social mobility. The current evidence addresses the effectiveness of arts interventions in improving illnesses. Little attention has been paid to the social value of creative wellbeing for the general population. This paper is a rapid review and evidence synthesis that aims to answer the question, 'What is the social value of place-based arts and culture interventions at individual (wellbeing) and community (social inequalities) levels in the UK and Europe?'. After a systematic search of five databases, search engines, and a call for evidence in August 2022, 14 out of 974 sources met the inclusion criteria. Studies were organised into three themes (Community, Events, Museums), and outcomes were analysed considering the indicators and dimensions of wellbeing (Office for National Statistics). The review evidenced that creative wellbeing leads to improvements in wellbeing outcomes and can contribute to alleviating social determinants of health. However, considering their impact on the underlying causes of structural social inequalities requires caution.

2.
Qual Health Res ; 31(6): 1019-1028, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33430718

RESUMEN

Congenital facial palsy is a rare medical condition that causes paralysis of the facial muscles, lack of facial expression, and an unusual appearance. Findings from developmental psychology suggest that the face plays a central role in the construction of self. Semi-structured interviews were conducted with 14 adults born with congenital facial palsy. Participant's constructions of self across the life span were explored and a grounded theory of this process was constructed. Theoretical sampling was conducted with two parents of children born with the condition. All participants reported "struggling to make connections," "experiencing invalidation," and "struggling to regulate affect," which lead to "constructing a defective sense of self." Alternatively, "making validating connections" facilitated the process of "constructing a validated sense of self." This study provides insight into the unique social and emotional challenges often experienced by those born with congenital facial palsy and highlights the need for early psychosocial intervention.


Asunto(s)
Parálisis Facial , Adulto , Niño , Emociones , Teoría Fundamentada , Humanos
3.
Plant Biotechnol J ; 17(4): 812-825, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30256508

RESUMEN

Chitin, a major component of fungal cell walls, is a well-known pathogen-associated molecular pattern (PAMP) that triggers defense responses in several mammal and plant species. Here, we show that two chitooligosaccharides, chitin and chitosan, act as PAMPs in grapevine (Vitis vinifera) as they elicit immune signalling events, defense gene expression and resistance against fungal diseases. To identify their cognate receptors, the grapevine family of LysM receptor kinases (LysM-RKs) was annotated and their gene expression profiles were characterized. Phylogenetic analysis clearly distinguished three V. vinifera LysM-RKs (VvLYKs) located in the same clade as the Arabidopsis CHITIN ELICITOR RECEPTOR KINASE1 (AtCERK1), which mediates chitin-induced immune responses. The Arabidopsis mutant Atcerk1, impaired in chitin perception, was transformed with these three putative orthologous genes encoding VvLYK1-1, -2, or -3 to determine if they would complement the loss of AtCERK1 function. Our results provide evidence that VvLYK1-1 and VvLYK1-2, but not VvLYK1-3, functionally complement the Atcerk1 mutant by restoring chitooligosaccharide-induced MAPK activation and immune gene expression. Moreover, expression of VvLYK1-1 in Atcerk1 restored penetration resistance to the non-adapted grapevine powdery mildew (Erysiphe necator). On the whole, our results indicate that the grapevine VvLYK1-1 and VvLYK1-2 participate in chitin- and chitosan-triggered immunity and that VvLYK1-1 plays an important role in basal resistance against E. necator.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Ascomicetos/fisiología , Quitina/análogos & derivados , Enfermedades de las Plantas/inmunología , Inmunidad de la Planta/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Vitis/enzimología , Arabidopsis/enzimología , Arabidopsis/genética , Arabidopsis/inmunología , Proteínas de Arabidopsis/genética , Quitina/metabolismo , Quitina/farmacología , Quitosano , Oligosacáridos , Filogenia , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Vitis/genética , Vitis/inmunología
4.
Neurosignals ; 27(S1): 20-31, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31778303

RESUMEN

BACKGROUND/AIMS: Multiple sclerosis (MS) is one of the most common autoimmune disorders of the central nervous system (CNS) and the leading cause of neurological disability among young adults in the Western world. We have previously shown that the acid sphingomyelinase plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. METHODS: We induced adoptively transferred EAE in wildtype and acid sphingomyelinase-deficient mice. In addition, we immunized mice with MOGaa35-55 to induce active EAE and treated the mice with amitriptyline, a functional inhibitor of the acid sphingomyelinase. We investigated symptoms of EAE, blood-brain barrier integrity and neuroinflammation. RESULTS: In the model of adoptively transferred EAE we demonstrate that expression of acid sphingomyelinase in the recipients rather than on transferred encephalitogenic T cells contributes to the clinical development of EAE symptoms. To test if pharmacological targeting of acid sphingomyelinase can be explored for the development of novel therapies for MS, we inhibited acid sphingomyelinase with amitriptyline in mice in which EAE was induced by active immunization. We demonstrate that pharmacological inhibition of acid sphingomyelinase using amitriptyline protects against the development of EAE and markedly attenuates the characteristic detrimental neuroinflammatory response. CONCLUSION: The studies identify the acid sphingomyelinase as a novel therapeutic target for treating MS patients.


Asunto(s)
Amitriptilina/uso terapéutico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/enzimología , Esfingomielina Fosfodiesterasa/antagonistas & inhibidores , Esfingomielina Fosfodiesterasa/deficiencia , Inhibidores de Captación Adrenérgica/farmacología , Inhibidores de Captación Adrenérgica/uso terapéutico , Amitriptilina/farmacología , Animales , Encefalomielitis Autoinmune Experimental/genética , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Esfingomielina Fosfodiesterasa/genética
5.
Int J Eat Disord ; 52(3): 278-282, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30706955

RESUMEN

OBJECTIVE: This study examined clinicians' views of the roles of two elements of cognitive behavioral therapy (CBT) in explaining treatment outcomes-CBT techniques and the therapeutic alliance. METHOD: Ninety-eight clinicians who reported delivering CBT for eating disorders completed measures addressing their beliefs about what is effective in CBT, their use of specific techniques, and their own anxiety levels. RESULTS: Clinicians substantially overestimated the role of both therapeutic techniques and the alliance in explaining treatment outcomes in CBT. Weak but significant correlations were found between therapist anxiety levels and their beliefs about the value of therapeutic techniques or the alliance. However, these associations were in different directions, with higher levels of clinician anxiety associated with more belief in the effects of the alliance but with less belief in the role of CBT techniques. Belief in the role of the therapeutic alliance was associated with a lower likelihood of encouraging the patient to change their eating pattern, while belief in the role of techniques was linked to greater use of case formulation, cognitive restructuring, behavioral experiments and body image work. DISCUSSION: Clinicians overestimate the value of both the alliance and therapy techniques in explaining treatment outcomes in CBT for eating disorders. Their beliefs about the strength of these factors are related to their own anxiety, and to their choice of techniques. Clinicians and supervisors should attend to the evidence regarding the impact of a range of elements of therapy, and work with all of those factors to enhance outcomes.


Asunto(s)
Terapia Cognitivo-Conductual/métodos , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Adulto , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Masculino , Alianza Terapéutica , Resultado del Tratamiento
6.
J Virol ; 91(2)2017 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-27852850

RESUMEN

The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes. IMPORTANCE: Herpesviridae is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins during virus replication. Our study focuses on two tegument proteins from herpes simplex virus 1 that are conserved in all herpesviruses: pUL7 and pUL51. We demonstrate that these proteins directly interact and form a functional complex that is important for both virus assembly and modulation of host cell morphology. Further, we identify for the first time that these conserved herpesvirus tegument proteins localize to focal adhesions in addition to cytoplasmic juxtanuclear membranes within infected cells.


Asunto(s)
ADN Helicasas/metabolismo , ADN Primasa/metabolismo , Herpes Simple/metabolismo , Herpes Simple/virología , Herpesvirus Humano 1/fisiología , Complejos Multiproteicos/metabolismo , Proteínas de la Matriz Viral/metabolismo , Proteínas Virales/metabolismo , Animales , Chlorocebus aethiops , ADN Helicasas/genética , ADN Primasa/genética , Regulación Viral de la Expresión Génica , Células HEK293 , Herpesvirus Humano 1/ultraestructura , Humanos , Unión Proteica , Transporte de Proteínas , Células Vero , Proteínas de la Matriz Viral/genética , Proteínas Virales/genética , Ensamble de Virus
7.
Neurosignals ; 25(1): 88-97, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29131010

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is a severe and common autoimmune disorder of the central nervous system. Despite the availability of several novel treatment options, the disease is still poorly controlled, since the pathophysiological mechanisms are not fully understood. METHODS: We tested the role of the acid sphingomyelinase/ceramide system in a model of MS, i.e. experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin-oligodendrocyte glycoprotein and the development of the disease was analyzed by histology, immunological tests and clinical assessment in wildtype and acid sphingomyelinase (Asm)-deficient mice. RESULTS: Genetic deficiency of acid sphingomyelinase (Asm) protected against clinical symptoms in EAE and markedly attenuated the characteristic detrimental neuroinflammatory response. T lymphocyte adhesion, integrity of tight junctions, blood-brain barrier disruption and subsequent intracerebral infiltration of inflammatory cells were blocked in Asm-deficient mice after immunization. This resulted in an almost complete block of the development of disease symptoms in these mice, while wildtype mice showed severe neurological symptoms typical for EAE. CONCLUSION: Activation of the Asm/ceramide system is a central step for the development of EAE. Our findings may serve to identify novel therapeutic strategies for MS patients.


Asunto(s)
Encefalomielitis Autoinmune Experimental/genética , Linfocitos/metabolismo , Esfingomielina Fosfodiesterasa/genética , Uniones Estrechas/fisiología , Animales , Barrera Hematoencefálica/metabolismo , Adhesión Celular/fisiología , Proliferación Celular/fisiología , Ceramidas/metabolismo , Encefalomielitis Autoinmune Experimental/metabolismo , Ratones , Ratones Noqueados , Glicoproteína Mielina-Oligodendrócito , Esfingomielina Fosfodiesterasa/metabolismo
8.
Cell Physiol Biochem ; 37(1): 269-75, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26302995

RESUMEN

BACKGROUND: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. METHODS: In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. RESULTS: In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. CONCLUSION: The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis.


Asunto(s)
Linfocitos T CD4-Positivos/patología , Movimiento Celular/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Inmunidad Innata/inmunología , Receptores de Lipopolisacáridos/inmunología , Receptores Inmunológicos/inmunología , Animales , Barrera Hematoencefálica/inmunología , Antígenos CD28/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígeno CTLA-4/inmunología , Adhesión Celular/inmunología , Células Endoteliales/inmunología , Células Endoteliales/patología , Femenino , Inflamación/inmunología , Inflamación/patología , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Médula Espinal/inmunología
9.
Plant Cell Rep ; 34(1): 167-77, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25315813

RESUMEN

KEY MESSAGE: Functional characterization of the Columbia root-knot nematode resistance gene R Mc1 ( blb ) in potato revealed the R gene-mediated resistance is dependent on a hypersensitive response and involves calcium. The resistance (R) gene R Mc1(blb) confers resistance against the plant-parasitic nematode, Meloidogyne chitwoodi. Avirulent and virulent nematodes were used to functionally characterize the R Mc1(blb)-mediated resistance mechanism in potato (Solanum tuberosum). Histological observations indicated a hypersensitive response (HR) occurred during avirulent nematode infection. This was confirmed by quantifying reactive oxygen species activity in response to avirulent and virulent M. chitwoodi. To gain an insight into the signal transduction pathways mediating the R Mc1(blb)-induced HR, chemical inhibitors were utilized. Inhibiting Ca(2+) channels caused a significant reduction in electrolyte leakage, an indicator of cell death. Labeling with a Ca(2+)-sensitive dye revealed high Ca(2+) levels in the root cells surrounding avirulent nematodes. Furthermore, the calcium-dependent protein kinase (CDPK), StCDPK4 had a higher transcript level in R Mc1(blb) potato roots infected with avirulent nematodes in comparison to roots infected with virulent M. chitwoodi. The results of this study indicate Ca(2+) plays a role in the R Mc1(blb)-mediated resistance against M. chitwoodi in potato.


Asunto(s)
Calcio/inmunología , Resistencia a la Enfermedad/inmunología , Genes de Plantas/inmunología , Enfermedades de las Plantas/inmunología , Solanum tuberosum/inmunología , Tylenchoidea/inmunología , Animales , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Resistencia a la Enfermedad/genética , Electrólitos/metabolismo , Regulación de la Expresión Génica de las Plantas/inmunología , Genes de Plantas/genética , Interacciones Huésped-Parásitos/inmunología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/parasitología , Proteínas de Plantas/genética , Proteínas de Plantas/inmunología , Proteínas de Plantas/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/inmunología , Raíces de Plantas/parasitología , Proteínas Quinasas/genética , Proteínas Quinasas/inmunología , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunología , Solanum tuberosum/genética , Solanum tuberosum/parasitología , Tylenchoidea/patogenicidad , Tylenchoidea/fisiología , Virulencia/inmunología
10.
BMC Musculoskelet Disord ; 16: 367, 2015 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-26612459

RESUMEN

BACKGROUND: Low back pain (LBP) is the world's leading cause of disability and yet poorly understood. Cross-national comparisons may motivate hypotheses about outcomes being condition-specific or related to cultural differences and can inform whether observations from one country may be generalised to another. This analysis of data from three cohort studies explored whether characteristics and outcomes differed between LBP patients visiting chiropractors in Sweden, Denmark and the UK. METHODS: LBP patients completed a baseline questionnaire and were followed up after 3, 5, 12 and 26 weeks. Outcomes were LBP intensity (0-10 scales) and LBP frequency (0-7 days the previous week). Cohort differences were tested in mixed models accounting for repeated measures. It was investigated if any differences were explained by different baseline characteristics, and interaction terms between baseline factors and nations tested if strength of prognostic factors differed across countries. RESULTS: The study sample consisted of 262, 947 and 453 patients from Sweden, Denmark and the UK respectively. Patient characteristics were largely similar across cohorts although some statistically significant differences were observed. The clinical course followed almost identical patterns across nations and small observed differences were not present after adjusting for baseline factors. The associations of LBP intensity and episode duration with outcome differed in strength between countries. CONCLUSIONS: Chiropractic patients with low back pain had similar characteristics and clinical course across three Northern European countries. It is unlikely that culture have substantially different impacts on the course of LBP in these countries and the results support knowledge transfer between the investigated countries.


Asunto(s)
Dolor de la Región Lumbar/epidemiología , Dolor de la Región Lumbar/terapia , Manipulación Quiropráctica/tendencias , Adolescente , Adulto , Anciano , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Internacionalidad , Estudios Longitudinales , Dolor de la Región Lumbar/diagnóstico , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Dimensión del Dolor/tendencias , Estudios Prospectivos , Suecia/epidemiología , Resultado del Tratamiento , Reino Unido/epidemiología , Adulto Joven
11.
Undersea Hyperb Med ; 42(5): 425-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26591982

RESUMEN

Pulmonary barotrauma can cause cerebral arterial gas embolism (CAGE) from pulmonary overdistension of alveoli forcing gas into the pulmonary vasculature. We report a case of CAGE in a man found to have occult pulmonary arteriovenous malformation (PAVM) and undiagnosed obstructive sleep apnea (OSA). A 46-year-old man was admitted to the hospital for an acute seizure and left-sided weakness, with telangiectasias on his lower lip and tongue. Brain-computed tomography (CT) showed gas emboli in the right hemisphere. Chest CT revealed a 1.8-cm PAVM in the posterior right costophrenic sulcus. A transthoracic echocardiogram showed no intracardiac shunt or patent foramen ovale. He was treated with phenytoin, lidocaine and hyperbaric oxygen. The PAVM was occluded with a detachable balloon followed by coil embolization. Polysomnography revealed severe obstructive sleep apnea, which was treated with CPAP. Seven years later, the patient was functioning at his pre-event baseline. We propose the CAGE was caused by high negative intrathoracic pressures while breathing against an obstructed upper airway, with air entrainment into the PAVM and subsequent arterialization.


Asunto(s)
Malformaciones Arteriovenosas/complicaciones , Embolia Aérea/etiología , Embolia Intracraneal/etiología , Arteria Pulmonar/anomalías , Venas Pulmonares/anomalías , Malformaciones Arteriovenosas/terapia , Embolia Aérea/terapia , Humanos , Oxigenoterapia Hiperbárica , Embolia Intracraneal/terapia , Masculino , Persona de Mediana Edad , Apnea Obstructiva del Sueño/diagnóstico
12.
BMJ Open ; 14(6): e081104, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38885992

RESUMEN

INTRODUCTION: The prevalence of multiple long-term conditions (M-LTCs) increases as adults age and impacts quality of life and health outcomes. To help people manage these conditions, complex behaviour change interventions are used, often based on research conducted in those with single LTCs. However, the needs of those with M-LTCs can differ due to complex health decision-making and engagement with multiple health and care teams. OBJECTIVES: The aim of this review is to identify whether current interventions are effective for people living with M-LTCs, and which outcomes are most appropriate to detect this change. METHODS: Five databases (MEDLINE, Embase, PsycINFO, CINAHL and Web of Science) were systematically searched, between January 1999 and January 2022, to identify randomised controlled trials evaluating effectiveness of behaviour change interventions in people with M-LTCs. Intervention characteristics, intervention effectiveness and outcome measures were meta-analysed and narratively synthesised. RESULTS: 53 eligible articles were included. Emotional well-being and psychological distress (depression and anxiety) outcomes were most amenable to change (emotional well-being: standardised mean difference (SMD) 0.31 (95% CI 0.04 to 0.58); depression psychological distress: SMD -0.45 (95% CI -0.73 to -0.16); anxiety psychological distress: SMD -0.14 (95% CI -0.28 to 0.00)), particularly for interventions with a collaborative care approach. Interventions targeting those with a physical and mental health condition and those with cognitive and/or behavioural activation approach saw larger reductions in psychological distress outcomes. Interventions that lasted for longer than 6 months significantly improved the widest variety of outcomes. CONCLUSION: Complex interventions can be successfully delivered to those with M-LTCs. These are most effective at reducing psychological distress in those with physical and mental LTCs. Further research is needed to identify the effective components of interventions for people with two or more physical LTCs and which outcome is most appropriate for detecting this change.


Asunto(s)
Terapia Conductista , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Terapia Conductista/métodos , Calidad de Vida , Afecciones Crónicas Múltiples/terapia , Afecciones Crónicas Múltiples/psicología
13.
J Am Med Inform Assoc ; 31(5): 1126-1134, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38481028

RESUMEN

OBJECTIVE: Development of clinical phenotypes from electronic health records (EHRs) can be resource intensive. Several phenotype libraries have been created to facilitate reuse of definitions. However, these platforms vary in target audience and utility. We describe the development of the Centralized Interactive Phenomics Resource (CIPHER) knowledgebase, a comprehensive public-facing phenotype library, which aims to facilitate clinical and health services research. MATERIALS AND METHODS: The platform was designed to collect and catalog EHR-based computable phenotype algorithms from any healthcare system, scale metadata management, facilitate phenotype discovery, and allow for integration of tools and user workflows. Phenomics experts were engaged in the development and testing of the site. RESULTS: The knowledgebase stores phenotype metadata using the CIPHER standard, and definitions are accessible through complex searching. Phenotypes are contributed to the knowledgebase via webform, allowing metadata validation. Data visualization tools linking to the knowledgebase enhance user interaction with content and accelerate phenotype development. DISCUSSION: The CIPHER knowledgebase was developed in the largest healthcare system in the United States and piloted with external partners. The design of the CIPHER website supports a variety of front-end tools and features to facilitate phenotype development and reuse. Health data users are encouraged to contribute their algorithms to the knowledgebase for wider dissemination to the research community, and to use the platform as a springboard for phenotyping. CONCLUSION: CIPHER is a public resource for all health data users available at https://phenomics.va.ornl.gov/ which facilitates phenotype reuse, development, and dissemination of phenotyping knowledge.


Asunto(s)
Registros Electrónicos de Salud , Fenómica , Fenotipo , Bases del Conocimiento , Algoritmos
14.
Science ; 385(6706): eadj1182, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39024449

RESUMEN

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third (n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Veteranos , Humanos , Masculino , Variación Genética , Estudios Longitudinales , Polimorfismo de Nucleótido Simple , Estados Unidos , United States Department of Veterans Affairs , Femenino
15.
Handb Exp Pharmacol ; (216): 421-30, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23563669

RESUMEN

Sphingolipids, the main component of cellular membranes, are cellular 'jack-of-all-trades', influencing a variety of functions including signal transduction, cell activation, membrane fluidity and cell-cell interactions.In the last few years, sphingolipids have begun to be investigated in the pathophysiology of major diseases of the brain, e.g. multiple sclerosis and dementia. Modulation of neuroinflammatory responses, such as lymphocyte behaviour, is a chance to intervene in the pathways that cause disease. There is much research still to be done in this field, but the prospect of treating previously untreatable medical conditions compels us onwards. Here, we review the current knowledge of the link between sphingolipids and neuroinflammation.


Asunto(s)
Encefalitis/metabolismo , Neuronas/metabolismo , Transducción de Señal , Esfingolípidos/metabolismo , Enfermedad Aguda , Animales , Enfermedad Crónica , Encefalitis/patología , Humanos , Neuronas/patología
16.
medRxiv ; 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37425708

RESUMEN

Genome-wide association studies (GWAS) have underrepresented individuals from non-European populations, impeding progress in characterizing the genetic architecture and consequences of health and disease traits. To address this, we present a population-stratified phenome-wide GWAS followed by a multi-population meta-analysis for 2,068 traits derived from electronic health records of 635,969 participants in the Million Veteran Program (MVP), a longitudinal cohort study of diverse U.S. Veterans genetically similar to the respective African (121,177), Admixed American (59,048), East Asian (6,702), and European (449,042) superpopulations defined by the 1000 Genomes Project. We identified 38,270 independent variants associating with one or more traits at experiment-wide P<4.6×10-11 significance; fine-mapping 6,318 signals identified from 613 traits to single-variant resolution. Among these, a third (2,069) of the associations were found only among participants genetically similar to non-European reference populations, demonstrating the importance of expanding diversity in genetic studies. Our work provides a comprehensive atlas of phenome-wide genetic associations for future studies dissecting the architecture of complex traits in diverse populations.

17.
New Phytol ; 196(1): 238-246, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22803660

RESUMEN

• Plant-parasitic cyst nematodes form a feeding site, termed a syncytium, through which the nematode obtains nutrients from the host plant to support nematode development. The structural features of cell walls of syncytial cells have yet to be elucidated. • Monoclonal antibodies to defined glycans and a cellulose-binding module were used to determine the cell wall architectures of syncytial and surrounding cells in the roots of Arabidopsis thaliana infected with the cyst nematode Heterodera schachtii. • Fluorescence imaging revealed that the cell walls of syncytia contain cellulose and the hemicelluloses xyloglucan and heteromannan. Heavily methyl-esterified pectic homogalacturonan and arabinan are abundant in syncytial cell walls; galactan could not be detected. This is suggestive of highly flexible syncytial cell walls. • This work provides important information on the structural architecture of the cell walls of this novel cell type and reveals factors that enable the feeding site to perform its functional requirements to support nematode development.


Asunto(s)
Arabidopsis/citología , Arabidopsis/parasitología , Pared Celular/metabolismo , Células Gigantes/parasitología , Raíces de Plantas/citología , Raíces de Plantas/parasitología , Tylenchoidea/fisiología , Animales , Epítopos/inmunología , Esterificación , Conducta Alimentaria/fisiología , Femenino , Células Gigantes/citología , Glucanos/metabolismo , Mananos/inmunología , Pectinas/metabolismo , Enfermedades de las Plantas/parasitología , Polisacáridos/metabolismo , Xilanos/metabolismo , Xilema/citología , Xilema/parasitología
18.
J Environ Manage ; 97: 22-7, 2012 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-22325579

RESUMEN

This study investigated the effects of reed and willow on bioremediation of landfill leachate in comparison with an unplanted control by measuring redox potential levels in the rhizosphere of microcosm systems in a greenhouse. Plants had a significant influence on redox potential relative to the plant-less system. Redox potential in the reed rhizosphere was anoxic (mean -102±85 mV), but it was the least negative, being significantly higher than in the willow (mean -286±118 mV), which had the lowest Eh. Redox potential fluctuated significantly in the willow rhizosphere during daylight hours, with large decreases in the morning. Levels of NH(4)(+) decreased significantly in the first day of the experiment and remained at similar low levels in all three variants for the next four weeks of the experiment. Following this removal of ammonia significant peaks in NO(2)(-) occurred in the control and reed tanks on the 1st day, and again on 14th day in the control tank up to 13 mg/dm(3). In the willow tank there was also one significant peak of NO(2)(-) in the first week, but only up to 0.5 mg/dm(3). Significant accumulation, within 21 days of NO(3)(-) in all variants was observed, but in tanks with reed and willow the concentration of NO(3)(-) remained significantly lower (<4 mg/dm(3)) than in the unplanted tank (∼35 mg/dm(3)). Final levels of total-nitrogen, nitrate and chemical oxygen demand were considerably lower in the reed and willow tank than in the unplanted tank.


Asunto(s)
Nitrógeno/metabolismo , Poaceae/metabolismo , Salix/metabolismo , Contaminantes Químicos del Agua/química , Humedales , Nitrógeno/análisis , Oxidación-Reducción , Poaceae/microbiología , Rizosfera , Salix/microbiología
19.
Angew Chem Int Ed Engl ; 51(20): 4921-4, 2012 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-22431324

RESUMEN

Light without fright: a synthetic route to fluorescent primary phosphanes (RPH(2)) that are resistant to air oxidation both in the solid state and in chloroform solution is described. These versatile precursors undergo hydrophosphination to give tripodal ligands and subsequently fluorescent transition-metal complexes.

20.
J Bodyw Mov Ther ; 30: 53-59, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35500979

RESUMEN

BACKGROUND: Reduced ankle dorsiflexion is associated with lower limb injury and dysfunction, with static stretching mostly used to increase ankle range of motion. Foam rolling is an alternative intervention, shown to immediately increase ankle range of motion, while the long-term application has conflicting evidence. AIMS: To assess the effects of single and multiple foam rolling interventions on ankle dorsiflexion range of motion in healthy adults and appraise the methodological quality of the included studies. DESIGN: Systematic literature review. METHODS: Five electronic databases were systematically searched to identify randomised controlled trials reporting the effects of foam rolling on ankle dorsiflexion. Data was extracted from studies that met the inclusion criteria and independently appraised by each reviewer using the PEDro scale. RESULTS: Thirty-two articles were identified; six studies included foam rolling compared to other interventions on ankle dorsiflexion range of motion. Five of the six studies reported a significant increase (p < 0.05) in ankle dorsiflexion within groups compared to baseline measurements, after a single foam rolling intervention. One study found a significant within group increase in long-term effects after foam rolling on ankle dorsiflexion over seven weeks. The mean PEDro score for all studies was 6/10 indicating a high-quality level of evidence. CONCLUSION: There is strong evidence suggesting that foam rolling may be effective in increasing range of motion in a healthy adult population in the short term up to 30 min; however, definitive conclusions on long-term effects cannot be drawn due to a lack of evidence, with further research recommended.


Asunto(s)
Tobillo , Ejercicios de Estiramiento Muscular , Adulto , Articulación del Tobillo , Humanos , Extremidad Inferior , Rango del Movimiento Articular
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